Effects of Age and Biological Age-Determining Factors on Telomere Length in Type 2 Diabetes Mellitus Patients.

Background and Objectives: Telomere length (TL) undergoes attrition over time, indicating the process of aging, and is linked to a higher risk of diabetes mellitus type 2 (DM-2). This molecular epidemiological study investigated the correlation between leukocyte TL variations and determinants of molecular aging in 121 Pakistani DM-2 patients. Materials and Methods: The ratio of telomere repeats to the SCG copy number was calculated to estimate the TL in each sample through qPCR assays. Results: In this study, smaller mean TLs were observed in 48.8% of males (6.35 ± 0.82 kb), 3.3% of underweight patients (5.77 ± 1.14 kb), 61.2% of patients on regular medication (6.50 ± 0.79 kb), 9.1% with very high stress levels (5.94 ± 0.99 kb), 31.4% of smokers (5.83 ± 0.73 kb), 40.5% of patients with low physical activity (6.47 ± 0.69 kb), 47.9% of hypertensive patients (5.93 ± 0.64 kb), 10.7% of patients with DM-2 for more than 15 years, and 3.3% of patients with a delayed onset of DM-2 (6.00 ± 0.93 kb). Conclusion: This research indicated a significant negative correlation (R2 = 0.143) between TL and the age of DM-2 patients. This study demonstrated that the correlation of telomere length with age in DM-2 patients was also influenced by various age-determining factors, including hypertension and smoking habits, with significant strong (R2 = 0.526) and moderate (R2 = 0.299) correlations, respectively; sex, obesity, the stress level and age at the onset of diabetes with significant weak correlations (R2 = 0.043, 0.041, 0.037, and 0.065, respectively), and no significant correlations of medication routine, rate of physical activity, and the durations of DM-2 with age-adjusted telomere length. These results challenge TL as the sole marker of aging, thus highlighting the need for further research to understand underlying factors and mitigate the effect of aging or premature aging on diabetic patients.

New molecular targets in Hodgkin and Reed-Sternberg cells.

Recent discoveries shed light on molecular mechanisms responsible for classical Hodgkin lymphoma (HL) development and progression, along with features of Hodgkin - Reed and Sternberg cells (HRS). Here, we summarize current knowledge on characteristic molecular alterations in HL, as well as existing targeted therapies and potential novel treatments for this disease. We discuss the importance of cluster of differentiation molecule 30 (CD30) and the programmed cell death-1 protein (PD-1) and ligands (PD-L1/2), and other molecules involved in immune modulation in HL. We highlight emerging evidence indicating that the altered function of SWI/SNF-type chromatin remodeling complexes, PRC2, and other epigenetic modifiers, contribute to variations in chromatin status, which are typical for HL. We postulate that despite of the existence of plentiful molecular data, the understanding of HL development remains incomplete. We therefore propose research directions involving analysis of reverse signaling in the PD-1/PD-L1 mechanism, chromatin remodeling, and epigenetics-related alterations, in order to identify HL features at the molecular level. Such attempts may lead to the identification of new molecular targets, and thus will likely substantially contribute to the future development of more effective targeted therapies.

Dissemination of NDM-1 in pseudomonas aeruginosa and klebsiella pneumoniae isolated from pus samples in tertiary care hospitals of Quetta, Pakistan.

OBJECTIVE: To highlight the prevalence and epidemiology of New Delhi metallo-ß-lactamase-1. producers in pus samples. METHODS: The cross-sectional study was conducted from April to August 2018 at the Biotechnology Laboratory, Balochistan University of Information Technology Engineering and Management Sciences, Quetta, Hi-tech Laboratory, Centre for Advance Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta and Microbiology Laboratory, Bolan Medical Complex Hospital, Quetta, Pakistan. Biochemical and molecular approaches were used for the identification of the isolates and Modified Hodge Test for the phenotypic detection of class-A carbapenemase activity. Minimum Inhibitory Concentration was performed using E-test and broth microdilution method. Molecular basis of carbapenemase activity was ascertained by the recognition of blaNDM-1 gene in the isolates. RESULTS: Of the 300 pus samples taken from surgical/burn units, 6(2%) blaNDM-1 harbouring isolates were found; 3(50%) each being Klebsiella pneumoniae and Pseudomonas aeruginosa. Klebsiella. pneumoniae isolates were extensively drug-resistant. The Pseudomonas aeruginosa isolates displayed resistance against 21 antibiotics of tetracyclines, quinolones, b-lactams, aminoglycosides, monobactams, sulphonamides, macrolides, cephalosporins, phosphonic acid and polypeptide groups, suggesting pan-drug resistance. CONCLUSIONS: The resistance pattern of the bacterial isolates poses a significant clinical threat in the region.